Atirmociclib

Atirmociclib : Inhibitor of CDK4, CDK6

Structure

SERP Rating

In Cells

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In Model Organisms

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Probe Atirmociclib is in the process of SERP review.

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Information

CDK4

Inhibitor

up to 1 uM

In Vitro Validations

Uniprot ID: P11802

Target Class: Kinase

Target SubClass: CMGC

Potency: Ki

Potency Value: 0.7 nM

Potency Assay: Biochemical assay using recombinant CDK4/cyclin D1

PDB ID for probe-target interaction (3D structure): 9CSK

Target aliases:

Cyclin-dependent kinase 4, CDK4, CDK4_HUMAN, PSK-J ...

DOI Reference: 10.1016/j.ccell.2025.02.006

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Biochemical assays with 265 recombinant kinases in in vitro enzymatic assays (CARNA) by 1 μM atirmociclib using ATP concentrations binned by KM for each kinase confirms its selectivity.

Potency assay, off target (cells): A set of 25 cell lines were tested with Atirmociclib and the following were found sensitive to treatment (IC50 <250 nM): MDAMB175VII, HCC1419, T47D-KBLUC, ZR751, CAMA1, BT474, HCC1500, MCF7, HCC1428

Potency assay (off target): in a biochemical Assay using recombinant CDK6- cyclin D3, CDK6 activity was 23 nM

Potency assay, off target (cells): IC50 of 2881 nM, assessing phosphorylation of RB1 at serine 807/811 from CDK4 independent human primary CD34+ hematopoietic stem and progenitor cells, treated for 24 h.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Atirmociclib is a CDK4-preferring inhibitor currently in clinical development by Pfizer, following the CDK4/6 unselective compound Palbociclib. Given its development stage, this molecule has been robustly characterized both in vitro and in vivo, with no concerns from an overall compound property perspective or broader selectivity profile. Currently, there are additional molecules in earlier stages of discovery and development that may offer greater selectivity of CDK4 over CDK6 and could, therefore, be preferable as chemical probes to specifically interrogate CDK4 biology over CDK6. However, these molecules have not been widely characterized or published to date. Until further characterization occurs, Atirmociclib may still be the best choice. With selectivity for CDK4/6 ranging from 15-35-fold, depending on the assay and publication, the prudent use of dose-response studies and the avoidance of 'high' compound concentrations is recommended. In summary, Atirmociclib may be the most characterized CDK4-preferring inhibitor to date, though a better chemical tool will likely become available in the near future.

(last updated: 16 May 2025 )